1. Field of the Invention
Angiogenesis is the process of increased vascularization in response to an angiogenesis factor. It occurs as a result of the endothelial cells in the existing blood vessels being stimulated into mitosis, thereby producing a new capillary network which advances towards its stimulus.
Solid tumors in situ are supported by an extensive vascular network which supplies the tumor with nutrients and eliminates its waste. This extensive vascular network is thought to develop from the host's normal and less extensive vascular network in response to the secretion of substances known as tumor angiogenesis factor.
Angiogenesis factors are not specific for tumors alone. Recently, an angiogenesis factor has been isolated from the joint fluid of patients suffering from the inflammatory disease, rheumatoid arthritis. This angiogenesis factor was isolated from the synovial fluid of the inflamed joint and was serologically identical with the tumor angiogenesis factor isolated from animals with experimental cancers. (Lancet 1, 682, Mar. 1980).
In addition, angiogenesis is associated with the pathological condition known as diabetic retinopathy and also with normal wound healing.
The present invention relates to antibodies specific for the human angiogenesis factor, angiogenin. The antibodies of the present invention bind to the human angiogenin molecule inhibiting its activity, thereby inhibiting angiogenesis. The antibodies of the present invention are useful agents for inhibiting angiogenesis in humans and other mammals such as in the treatment of tumors, diabetic retinopathy, inflammatory diseases, and disease states where angiogenesis is not desired.
2. Description of the Related Art
LeVeen, U.S. Pat. No. 4,529,590, describes a method for producing a bovine angiogenesis factor. LeVeen's method consists of inducing a prolonged inflammatory response in the cattle secondary to the injection of irritants into the body cavity of the animal. The angiogenic material which LeVeen isolated from fluid at the site of irritation was only partially characterized; it tested positive for angiogenic activity on chick chorioallantoic membrane and was capable of evolving an immune response in animals but is distinguished from angiogenin by having an isoelectric point low enough to allow chromatography on an anion exchanger, such as DEAE cellulose.
Vallee et al., U.S. patent application Ser. No. 778,387 filed Sep. 20, 1985, hereby incorporated by reference described purification and characterization of angiogenin, an angiogenic protein from human adenocarcinoma cell line HT-29. Angiogenin was also described in Fett et al., Biochemistry, Vol. 24, pp. 5480-5486, (1985).
The present invention relates to antibodies specific to human angiogenin, and to therapeutic compositions containing them as well as their use in inhibiting angiogenesis in mammals.